Figure 4
Peptidomimetics emulating the Plk1-PBD·Emi2 complex inhibit maturation of mouse oocytes.
(A) Peptidomimetics resemble Plk1-PBD·Emi2 and bind to the Polo box domain (PBD) of Plk1. The compounds 103, 103-2, 103-5, 103-8, 103-10, 103-12, 103-13, 103-15 and 103-16 have been described previously34 and 699, 700, 701, 702, 703, 704, 705, 706 and 707 were characterized in this study. (B) Assessment of inhibitory activity of peptidomimetics on in vitro maturation (IVM) of mouse oocytes. Peptidomimetics were microinjected into immature mouse oocytes, which were subjected to IVM. GV: germinal vesicle, GVBD: germinal vesicle breakdown, MI: metaphase I, MII: metaphase II. Time (hr) required for maturation of an oocyte is indicated at the top of an arrow. Maturation status of mouse oocytes 12 hr after injection of a peptidomimetic was evaluated. At least three independent experiments were carried out and the ratios of oocytes at each developmental stage to all oocytes were plotted. Significant differences between the treatment groups and the control group are indicated by asterisk (***P ≤ 0.001, **P ≤ 0.01, *P ≤ 0.05). (C) Crystal structure of the Plk1-PBD·702 complex. PBD domain is shown in blue and peptidomimetic 702 is shown in green. In the enlarged circle, the structures of Emi2169–177 (violet) and peptidomimetic 702 (Green) are superimposed. Note that occupation of tyrosine-rich pockets by an alkylated imidazole ring (702) or a phenylalanine ring (Emi2169–177).
